United States Patent 0
1
1
3,450,597
CO
3,450,597
Patented June 17, 1969
2
degree of purity and by an extremely reproducible proc
ess. A further object of this invention is to provide a
process which avoids the need for separating radioactive
products and other impurities. These and other objects
Henry H. Kramer, Mahwah, N.J., and Hirofumi Arino,
will readily become apparent to those skilled in the art
Su?ern, N.Y., assignors to Union Carbide Corporation,
in the light of the teachings herein set forth.
a corporation of New York
It has now been discovered that the aforementioned
No Drawing. Filed Dec. 23, 1966, Ser. No. 604,152
Int. Cl. G21g 1/02
objects can be achieved by a process which comprises
U.S. Cl. 176-16
9 Claims
the steps of (a) irradiating a tin compound, (b) dissolv
10 ing the tin compound, (c) diluting the dissolved tin com
PRODUCTION OF HIGH PURITY RADIOACTIVE
INDIUM-113m
ABSTRACT OF THE DISCLOSURE
A process for producing radioactive indium-113m by
pound with water, (d) contacting the diluted tin solution
with silica gel, (e) selectively extracting indium-113m
from the silica gel substrate with dilute acid.
Operating in the aforesaid manner provides a selective
eluting from neutron irradiated tin that is retained on a 15 separation of indium-113m from all other elements in the
silica gel substrate.
dissolved tin compound with very high ef?ciency, i.e.,
over 90 percent. In addition the process of this invention
is readily reproducible and simple to operate.
This invention relates to a novel process for the pro
duction of radioactive indium-113m. In one aspect, this
invention relates to a novel process for the production of
radioactive indium-113m in high yields. A further aspect
Although a variety of tin compounds are suitable for
use in the process of this invention the preferred tin target
is thin metal. Particularly preferred is tin metal enriched
in the stable tin-112 isotope. In the event that tin com
pounds other than tin metal are employed, it is preferred
to isolate the tin component after irradiation. Illustrative
of this invention is directed to a novel process for the
production of radioactive indium-113 which can be ob
tained in a high ‘degree of purity.
25 tin compounds which can be employed as the source of
Recent medical investigation has shown that indium
ll3m is an extremely useful tool for diagnosis. High purity
tin include, among others, tin metal, tin oxide, tin nitrate,
indium-113m is used primarily as a radioisotope in a
and the like.
Irradiation of the tin compound by neutrons is a Well
tin sulfate, organic tin compounds such as tetraphenyl tin,
variety of medical research and diagnosis. It is well suited
for liver, lung, blood pool and tumor scanning, and is 30 known technique and can be effected by placing the tin
preferred over other radioactive isotopes because of its
short half-life which results in reduced exposure of the
organs to radiation. In addition to medical uses, indium
113m can also be employed in industrial applications,
compound in the irradiation zone of a nuclear reactor,
neutron generator, or‘ neutron isotopic source.
Thereafter, the irradiated tin compound is dissolved
in a suitable solvent. In the case of tin metal, concen
such as in the measurement of ?ow rates, process control, 35 trated hydrochloric acid is employed. For other tin com
radiometric chemistry, and the like. Since the radioisotope
pounds it may be necessary to employ a basic solvent
sought to be used has such ‘a short half-life, it is com
such as sodium hydroxide and perform additional reac
mon practice to ship the users of the isotope the parent
tions to isolate the tin.
element; in this case neutron irradiated tin. The user then
It has ‘been found to be advantageous to dissolve the
extracts the indium-113m from the tin as his needs require. 40 tin metal in hydrochloric acid in the presence of an oxi
The production of indium-113m and its decay is illustrated
dizing agent to aid in the dissolution and to insure that
as follows:
the tin is in the stannic (+4) oxidation state. Hydrogen
is preferred inasmuch as it is easily removed from the tin
112811 (n, 'y)113Sn">113mIn_)113In (Stable)
where 113sn is obtained by neutron irradiation of 112sn;
113sn decays by the electron capture process to 113mln
with the half-life of 118 days; 113mm, a metastable iso
tope, decays to the ground state, 1131“, by the isomeric
transition process with the half-life of 104 minutes.
In the past, radioactive indium-113m has been produced
by a variety of methods. For example, I. Stonski and
V. N. Pybakov (Chemia Analityczna, 4, 877, 1959) pre
solution by heating. Other oxidants such as bromine water,
45 permanganate, and the like, can be used but are less
preferred.
Thereafter the dissolved tin compound is diluted with
water in the presence of a drop or two of bromine water
to insure the proper oxidation state (+4) of the tin. The
50 solution is adjusted to provide a tin concentration in 0.3
to 0.5 molar HCl of at least about 0.5 milligram of tin,
as the element, per milliliter of solution.
Silica gel is then immediately contacted with the dilute
pared an indium-113m generator using an anion exchange
acid solution containing the tin. The preferred mesh is
resin. The indium-113m was eluted with 3 molar hydro 55 from 20to 200. The silica gel can be added to a vessel
chloric acid. The radiochemical purity of indium-113m
containing the tin solution until thoroughly wet and then
was approximately 99‘ percent. The indium-113m solution
heated to enhance the deposition of the tin on the gel.
thus obtained was not suitable for medical formulation
Preferably the solution is heated to about 40° to 100° C.
because of the strong acid strength, the signi?cant tin-113
and
more preferably 80° C. from 15 to 20 minutes fol
breakthrough and the possible contamination by the radi 60
lowed by digestion at room temperatures for not less than
ation degradation products of the organic resin. Another
about two hours.
type of generator developed in the Oak Ridge National
Alternatively, the solution can be left at room tem
Laboratory used hydrous zirconium oxide as the adsorber
perature for a long period of time. However, the amount
of tin-113 from which indium-113m was eluted with
methyl ethyl ketone.
65 of tin deposited has been shown not to be reproducible,
and may take as long as several weeks.
However, to date, none of the work reported in litera
The silica gel containing the tin is then transferred to
ture has been entirely successful in the development of an
an appropriate elution system such as a column, prefer~
indium-113m‘ generator ‘which meets present day medical
requirements. It is therefore an object of this invention to
ably glass, or other inert material. The supernatant liquid
provide a more e?icient method for producing radioactive 70 is allowed to drain and the substrate washed with ap
indium-113m. Another object of this invention is to pro
proximately 10 to 200- milliliters of 0.01 to 0.1 molar
vide a process for preparing radioactive indium in a high
HCl, more preferably 0.07 molar IHCl.
3,450,597
3
4
The loaded column which contained 1l3mSn-l13m1n ac
tivity can subsequently be eluted or milked repeatedly for
113mln as it is formed with an acidic solution. Preferably,
it has been observed that best results are obtained when'
the column is eluted with 4 to 20 milliliter portions of
’ Radiometric analysis of the eluted "indium-113m indi
cates that it contains 95 percent of the available indium
113m and the radionuclidic purity is greater than 99.98
percent. The total metal element impurity is less than 1
part per million as determined by emission spectroscopy
0.03 to 0.1 molar HCl solution. This is done by passing
the desired volume of HCl through the column and col-,
techniques.
.
The substrate and/or the entire elution system can be
sterilized by acceptable autoclave techniques with no re
duction in radionuclidic impurity, no increase in the metal
Numerous variations of the preferred embodiment de
scribed above may be practiced, as will be apparent to 10 element impurities and only a slight reduction in the
amount of indium-113m recoverable.
those skilled in the art, without departing from the basic
Although the invention has been illustrated by the pre
concepts of the present invention.
ceding example, it is not to be construed as being limited
As previously indicated, the process of the present in
to the materials employed therein, but rather, the inven
vention provides a simple, method for the preparation of
indium-113m in a high degree of efficiency. By this proc 15 tion encompasses the generic area as hereinbefore dis
closed. Various modi?cations and embodiments of this
ess recovery of indium-113m can be effected with hydro
invention can be made without departing from the spirit
chloric acid in e?iciencies of 90% and higher, over a pH
lecting the e?iuent.
and scope thereof.
What is claimed is:
range of about 0.5 to about 1.7 without appreciable disso
lution of the silica gel or removal of any tin from the
silica gel substrate.
A further advantage characteristic of the process of this
invention, is that the substrate and/or the entire elution
system can be sterilized, i.e., by autoclaving at the nor
mally prescribed temperatures and pressures.
In contrast, the previously known hydrous zirconium
20
oxide, which can also be loaded by the above-described
1. A :process for producing radioactive indium-113m
which comprises the steps of:
(a) irradiating a tin containing material in a neutron
flux until the desired amount of tin-113 is formed;
(b) dissolving the irradiated tin containing material
containing the radioactive tin-113, to obtain a tin
solution;
{
procedure, has elution e?iciencies greater than 50 percent
and normally less than 75 percent when eluted with hy
(c) diluting the tin solution with water;
(d) contacting silica gel with said dilute tin solution,
drochloric acid over a pH range of about 1.4 to about
heating to a temperature of from about 40° to about
1.6. A lower pH than 1.4 would result in appreciable 30
dissolution of the zirconium oxide, while a higher pH
results in decreased e?iciencies. Under optimum elution
conditions of both substrates, the major advantages of
the present process are (a) higher e?iciency of recovery
of indium-113m from the substrate, (b) greater operat
ing pH range over which el?cient elution can be effected,
and (c) sterilization of the substrate by normal auto~
claving methods, i.e., steam and pressure, only slightly
reduces the recoverable indium-113m, for example about
5 percent for the silica gel substrate as compared to about
20 to about 30 percent for the zirconium oxide substrate.
The following example is illustrative:
Example I
100° C., thereby loading the tin on said silica gel
to provide an elution system, and
(e) selectively extracting said elution system with a
solution consisting essentially of a dilute inorganic
acid at a pH range of from about 0.5 to about 1.7
to separate indium-113 from its radioactive parent
tin-113 that is deposited on the silica gel.
2. The process of claim 1 wherein said tin containing
material is tin metal.
3. The process of claim 1 wherein said tin containing
material is tin metal enriched in the stable tin-112 iso
tope.
4. The process of claim 1 wherein said irradiated tin
containing material is dissolved in concentrated hydro
Tin metal (500 milligram) enriched in tin 112 is en 45 chloric acid in the presence of an oxidizing agent.
5. The process of claim 1 wherein said tin solution
capsulated in high purity quartz tubing which is then in
turn secondarily encapsulated in aluminum tubing. The
is diluted to a minimum tin concentration of at least 0.5
milligram per milliliter of 0.3 to 0.5 molar hydrochloric
container is then placed in a nuclear reactor neutron irradi
acid.
ation zone of a high thermal neutron ?ux. The capsule
was irradiated for approximately 500 to 5000 hours. The 50
6. The process of claim 1 wherein said diluted tin
container is removed from the radiation zone to an
solution is contacted with said silica gel and heated at a
‘appropriate shielded facility. The tin is removed from its
temperature of from about 40° to 100° C., and then al
encapsulation material, dissolved in concentrated HCl
lowed to stand at room temperature.
which contains several drops of hydrogen peroxide (30
7. The process of claim 1 wherein indium-1 13111. is se
percent) thereafter, the concentration was adjusted to 10 55 lectively extracted with hydrochloric acid of a concen
milligrams of tin per 1 milliliter of 4 molar HCl. Prior
tration of from about 0.01 to 0.1 molar.
to loading, the above solution was diluted 10:1 with water
8. The process of claim 1 wherein said elution system
containing a few drops of bromine water. Approximately
is sterilized.
20 milligrams of tin (20 milliliters of the diluted solution)
9. The process of claim 8 wherein said sterile elution
is loaded on 5 milliliters wet volume of silica gel (ap 60
system is extracted with sterile hydrocholric acid to pro
proximately 4 grams) by contacting the silica gel with
vide a sterile solution containing irradiated indium-113m.
the solution for 15 to 20 minutes at 80° C. followed by
2 to 24 hours at room temperature. The silica gel solution
No references cited.
is then loaded to a glass column 1 x 5 centimeters which
is shielded with an appropriate lead container. The super 65
BENJAMIN R. PADGETT, Primary Examiner.
nate is permitted to drain and the silica gel washed with
125 milliliters of 0.07 molar HCl. After an appropriate
H. E. BEHREND, Assistant Examiner.
time period to permit the decay of the retained tin-113
U.S. Cl. X.R.
to indium-113m the available indium-113m on the col
umn is removed by the addition of 5 milliliters of 0.07 70 210-38; 252-3011
molar HCl.